Fosphenytoin: Pharmacokinetics and Tolerance of Intramuscular Loading Doses

Summary: Purpose: Fosphenytoin (FPHT; Cerebyx) is well absorbed when given intramuscularly (IM). All prior pharmacokinetic studies had the first plasma sample obtained 30 min after IM administration. The objectives of this study were to determine the rate and extent of FPHT absorption and to evaluate the tolerability of IM FPHT compared with IM saline.

Methods: This was an open-label, double-blinded study in which patients received 10 mg/kg dose of IM FPHT in one gluteus and IM saline in the other gluteus. Half the patients received saline injection of equal volume to FPHT (up to 19.5 mL); the other half received 2 mL of saline. Neurologic examination, vital signs, PHT blood samples, injection site examination, and subjective pain scores at injection site were obtained before and at timed intervals for 6 h.

Results: Total PHT serum concentrations 10 μg/mL were obtained in 5 min in 14.3% of patients and in 26.3% after 10 min. More than half the patients had therapeutic serum concentrations at 30 min; 45.8% of patients reported no pain at either the FPHT or saline injection site. No significant difference in pain was noted between FPHT and saline injection sites at 60 min and thereafter. Early decrease in blood pressure occurred but was not clinically significant. Classic PHT-induced central nervous system (CNS) side effects were evident in one third of patients within 1 h after injection.

Conclusions: (a) IM FPHT is rapidly absorbed (therapeutic levels achieved as early as 5–20 min). (b) IM FPHT is well tolerated by most patients irrespective of injection volume.